High-risk HPV E6 self-assemble into large stable oligomers that allow localization of endogenous oncoproteins in HPV transformed cell lines and HPV induced carcinoma.

MARÍA M. GARCÍA-ALAI, KARINA I. DANTUR, CLARA SMAL, ANGELES HEER AND GONZALO DE PRAT-GAY.

Prague, the Czech Republic

Conferencia; 23rd Papillomavirus Conference and Clinical Workshop; 2006

International Papillomavirus Society

The E6 oncoproteins of high-risk HPV types 16 and 18 are involved in the development of cervical cancer. Besides its determinant role in carcinogenic progression, HPV E6 oncoprotein has also been instrumental in elucidating fundamental aspects of p53 function and its ubiquitin-proteasome degradation, with counterpart activities in various DNA tumour viruses.  Establishing the conformational state and cellular distribution unequivocally for the endogenous protein in transformed cells and infected tissue is essential for understanding the underlying mechanism. Recombinant E6 from high-risk strains 16 and 18 fold into soluble oligomers of ~1.2 MDa, and antibodies against these forms locate E6 in the cytoplasm.  The same antibodies locate monomeric forms in the nucleus of Hela and CaSki cells, correlating with p53 degradation activity.  However, in cervical carcinoma, E6 is located in the cytoplasm and apical regions only, in agreement with the reported localization for E6’s PDZ domain targets, suggesting that this would be a main mechanism operating in pre-invasive carcinoma. In addition, our results suggest the possible use of specific antibodies against high-risk E6 as early diagnostic tools of significant prognostic value in cervical cancer.